The multiple genetic markers (allotypes and idiotypes) of rabbit antibodies will be employed in studies on the inheritance of antibody V regions and relationships between structural genes and immune responsiveness. The possibility that multiple genes code for the VH region can be examined because the deteminants of both VH region allotypes and idiotypes are in the antibody V region. Breeding studies will be carried out to determine if a recently observed amino acid substitution in the VL region of homogeneous antibodies and IgG can serve as a VL genetic marker. Allotype-idiotype linkage studies may be extended to the VL region by use of this VL marker. Examination of the group a allotypic specificities on a panel of homogeneous antibodies has revealed that each antibody displays only a portion of the specificities present in a total IgG fraction of the given allotype. One explanation for this observation is that the allotypic determinants of a given (a) allele include a finite number of structural variants. Another possibility is that this diverse expression is caused by modulation of the allotypic specificity by binding site components. These possibilities will be examined by structural and serological studies. Specificities of group b allotypes will be further examined for evidence of heterogeneity. Studies in progress on the relationship between immune responsiveness and structural genes indicate that the b9 allotype is not expressed in the respones of a heterozygous (b4,9) rabbit after streptococcal immunization. The immune response of the b9 homozygote is, however, as great as that of b4 or b4,9 siblings. The reason for this allotypic selection in the synthesis of anti-streptococcal antibodies in heterozygotes is unknown. Studies will be carried out to determine whether structural features of their VL regions confer a selective advantage on the b4 allotype over the b9.